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| Open AccessNon-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes
Studies in animal models have visualized drainage of interstitial or cerebrospinal fluid via lymphatic vessels, but there is limited data on in humans. Here, the authors non-invasively visualize lymphatic structures in the human brain, including evidence of lymphatic flow from cranial nerves to cervical lymph nodes, and differences by age and sex, without use of contrast agents.
- Mehmet Sait Albayram
- , Garrett Smith
- & Onder Albayram
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| Open AccessRapid antigen testing as a reactive response to surges in nosocomial SARS-CoV-2 outbreak risk
Healthcare facilities are vulnerable to SARS-CoV-2 introductions and subsequent nosocomial outbreaks. Here, the authors simulate transmission in a long-term care facility with varying containment measures in place and evaluate reactive response with antigen rapid diagnostic testing.
- David R. M. Smith
- , Audrey Duval
- & Laura Temime
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| Open AccessSystematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database
Multiple drugs have been in the past associated with myocarditis. Here the authors perform a pharmacovigilance study and analyze 5108 reports of drug-induced myocarditis reporting temporal trends and overall mortality and identifying emerging drug classes among the treatments associated with myocarditis.
- Lee S. Nguyen
- , Leslie T. Cooper
- & Joe-Elie Salem
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| Open AccessA machine and human reader study on AI diagnosis model safety under attacks of adversarial images
While active efforts are advancing medical AI model development and clinical translation, safety issues of medical AI models have emerged. Here, the authors investigate the effects on an AI model and on human experts of potential fake/adversarial images for breast cancer diagnosis.
- Qianwei Zhou
- , Margarita Zuley
- & Shandong Wu
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Article
| Open AccessA low-cost and shielding-free ultra-low-field brain MRI scanner
A low cost MRI scanner may have the potential to meet clinical needs at point of care or in low and middle income countries. Here the authors describe a low cost 0.055 Tesla MRI scanner that operates using a standard AC power outlet, and demonstrate its preliminary feasibility in diagnosing brain tumor and stroke.
- Yilong Liu
- , Alex T. L. Leong
- & Ed X. Wu
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| Open AccessThe effect of COVID-19 vaccination in Italy and perspectives for living with the virus
Vaccination campaigns against COVID-19 are allowing the progressive release of physical distancing restrictions in many countries. Here, the authors assess the impact of the vaccination program in Italy and evaluate possible prospects for reopening the society while at the same time keeping COVID-19 under control.
- Valentina Marziano
- , Giorgio Guzzetta
- & Stefano Merler
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| Open AccessIncreased transmissibility of SARS-CoV-2 lineage B.1.1.7 by age and viral load
Establishing the relative transmissibility of emerging variants of SARS-CoV-2 is key for pandemic management. Here, the authors use full-population administrative data from Denmark linked to PCR test results and estimate that the Alpha variant was ~60% higher than other strains circulating in early 2021.
- Frederik Plesner Lyngse
- , Kåre Mølbak
- & Carsten Thure Kirkeby
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| Open AccessSerological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England
The UK extended the interval until the second COVID-19 vaccine dose up to 12 weeks. Here, the authors show in a cohort of 750 participants aged 50–89 years that the extended schedule results in higher antibody titers and estimate a higher vaccine effectiveness for the extended schedule.
- Gayatri Amirthalingam
- , Jamie Lopez Bernal
- & Mary E. Ramsay
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| Open AccessA deep learning framework identifies dimensional representations of Alzheimer’s Disease from brain structure
Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.
- Zhijian Yang
- , Ilya M. Nasrallah
- & Balebail Ashok Raj
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Article
| Open AccessPaper microfluidic implementation of loop mediated isothermal amplification for early diagnosis of hepatitis C virus
Current HCV nucleic acid-based diagnosis is largely performed in centralised laboratories. Here, the authors present a pan-genotypic RNA assay, based on reverse transcriptase loop mediated isothermal amplification and develop a low-cost prototype paper-based lateral flow device for point-of-care use, providing a visually read result within 40 min.
- Weronika Witkowska McConnell
- , Chris Davis
- & Jonathan M. Cooper
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| Open AccessChanges in notifiable infectious disease incidence in China during the COVID-19 pandemic
Non-pharmaceutical interventions implemented to mitigate COVID-19 transmission are likely to have impacted spread of other infectious diseases. Here, the authors investigate changes in the incidence of 31 notifiable infectious diseases using surveillance data from China.
- Meng-Jie Geng
- , Hai-Yang Zhang
- & Wei Liu
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Article
| Open AccessRisk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test
Identification of febrile children at risk of death in low-resource settings can improve survival, but tools for their prompt recognition are lacking. Here, the authors show that sTREM-1 measured at clinical presentation predicts in-hospital mortality in febrile children in Uganda.
- Aleksandra Leligdowicz
- , Andrea L. Conroy
- & Kevin C. Kain
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Article
| Open AccessImprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance
Maternal obesity predisposes offspring to obesity and metabolic disorders through incompletely understood mechanisms. Here the authors report that Dio3os is an imprinted long-coding RNA that modulates brown adipose tissue development and obesity resistance in the offspring.
- Yan-Ting Chen
- , Qi-Yuan Yang
- & Min Du
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| Open AccessAdaptation, spread and transmission of SARS-CoV-2 in farmed minks and associated humans in the Netherlands
SARS-CoV-2 was detected in mink farms in the Netherlands in the first wave of the pandemic with evidence of human-to-mink and mink-to-human transmission. Here, the authors investigate this outbreak using phylodynamic analysis and show that personnel links and spatial proximity are predictors of transmission between farms.
- Lu Lu
- , Reina S. Sikkema
- & Marion P. G. Koopmans
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Article
| Open AccessBST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities
Nicotinamide riboside (NR) is a NAD + precursor exhibiting beneficial effects against aging. Here the authors demonstrate that orally administered NR increases NAD + levels in a diphasic manner and that bone marrow stromal cell antigen 1 plays a crucial role for NAD + synthesis from NR.
- Keisuke Yaku
- , Sailesh Palikhe
- & Takashi Nakagawa
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| Open AccessAge-seroprevalence curves for the multi-strain structure of influenza A virus
Multi-strain pathogens, such as influenza, present challenges for interpretation of seroprevalence data as estimates may vary by strain. Here, the authors develop a method for estimating age-specific seroprevalence based on principal components analysis and apply it to influenza data from Vietnam.
- Dao Nguyen Vinh
- , Nguyen Thi Duy Nhat
- & Maciej F. Boni
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| Open AccessThe reduction of race and gender bias in clinical treatment recommendations using clinician peer networks in an experimental setting
Race and gender bias in healthcare contribute to health disparities. Here the authors show in an experimental setting that structured information sharing networks among clinicians can reduce race and gender bias in medical decisions.
- Damon Centola
- , Douglas Guilbeault
- & Jingwen Zhang
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| Open AccessBurdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status
Post-acute sequelae of COVID-19 (PASC, or ‘Long COVID’) has caused concern but the burden and risk factors are not well understood. Here, the authors use US electronic health record data and estimate an overall burden of PASC of ~7% at six months, with variation by severity of acute infection, baseline health status and demographics.
- Yan Xie
- , Benjamin Bowe
- & Ziyad Al-Aly
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| Open AccessA novel SARS-CoV-2 related coronavirus in bats from Cambodia
In this study, Delaune et al., isolate and characterise a SARS-CoV-2-related coronavirus from two bats sampled in Cambodia. Their findings suggest that the geographic distribution of SARS-CoV-2-related viruses is wider than previously reported.
- Deborah Delaune
- , Vibol Hul
- & Veasna Duong
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| Open AccessHigher intake of whole grains and dietary fiber are associated with lower risk of liver cancer and chronic liver disease mortality
Higher intake of dietary fiber and whole grains are associated with reduced risk of various diseases including some cancers. Here, the authors estimate reductions in liver cancer of 22% and 31% and chronic liver disease mortality of 56% and 63% associated with increased whole grain and dietary fiber intake, respectively.
- Xing Liu
- , Wanshui Yang
- & Xuehong Zhang
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| Open AccessPotential global impacts of alternative dosing regimen and rollout options for the ChAdOx1 nCoV-19 vaccine
The ChAdOx1 nCoV-19 vaccine requires two doses, but under limited supply single dose regimens have also been considered. Here, the authors show using static transmission modelling that under certain conditions it is optimal to more expediently administer a single dose to a larger proportion of the population.
- Ricardo Aguas
- , Anouska Bharath
- & Rima Shretta
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| Open AccessHepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates
Pompe disease is currently treated with enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (GAA). Here, the authors show hepatic-directed gene therapy with AAV vectors enhances GAA bioavailability compared with ERT, resulting in improved rescue of the disease phenotype in mice and broad enzyme distribution in mice and non-human primates.
- Helena Costa-Verdera
- , Fanny Collaud
- & Federico Mingozzi
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| Open AccessUsing secondary cases to characterize the severity of an emerging or re-emerging infection
Estimates of the severity of emerging infections did not consider the case ascertainment method, but secondary cases identified by contact tracing of index cases may be more reliable as they are less susceptible to ascertainment bias. Here, the authors perform a systematic review to quantify these differences and model their impacts for COVID-19.
- Tim K. Tsang
- , Can Wang
- & Benjamin J. Cowling
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| Open AccessUnderstanding how Victoria, Australia gained control of its second COVID-19 wave
The state of Victoria, Australia experienced a substantial second wave of COVID-19 but brought it under control with strict non-pharmaceutical interventions. Here, the authors model the second wave in Victoria to estimate the impacts of the different interventions.
- James M. Trauer
- , Michael J. Lydeamore
- & Romain Ragonnet
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| Open AccessClinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa
Cost, supply and logistics present challenges to COVID-19 vaccine rollout in low and middle income countries. Here, the authors model vaccination programmes in South Africa and demonstrate the importance of the pace of vaccine rollout, with even moderately efficacious vaccines likely to be cost-effective.
- Krishna P. Reddy
- , Kieran P. Fitzmaurice
- & Mark J. Siedner
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Article
| Open Access3D printed biomimetic cochleae and machine learning co-modelling provides clinical informatics for cochlear implant patients
Current spread hampers the efficacy of neuromodulation, while existing animal, in vitro and in silico models have failed to give patient-centric insights. Here the authors employ 3D printing and machine learning to advance clinical predictions of current spread for cochlear implant patients.
- Iek Man Lei
- , Chen Jiang
- & Yan Yan Shery Huang
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| Open AccessThe impact of the timely birth dose vaccine on the global elimination of hepatitis B
The timely hepatitis B birth dose vaccination is recommended for all new-borns by the WHO, but coverage is inconsistent. Here, the authors model the impact of scaling-up coverage in 110 low and middle income countries and assess how it may be affected by delays for example caused by the COVID-19 pandemic.
- Margaret J. de Villiers
- , Shevanthi Nayagam
- & Timothy B. Hallett
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| Open AccessUnderstanding the effectiveness of government interventions against the resurgence of COVID-19 in Europe
European governments control resurging waves of COVID-19 using nonpharmaceutical interventions. Here, the authors estimate the effectiveness of 17 interventions in Europe’s second wave, and analyse differences to the first wave as well as implications for the future of the pandemic.
- Mrinank Sharma
- , Sören Mindermann
- & Jan Markus Brauner
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| Open AccessGenomic sequencing of SARS-CoV-2 in Rwanda reveals the importance of incoming travelers on lineage diversity
Genomic surveillance of SARS-CoV-2 can inform regional transmission dynamics and inform public health interventions. Here, the authors sequence ~200 samples from Rwanda, identify shifts in predominating strains from May 2020 to February 2021, and infer geographic origins.
- Yvan Butera
- , Enatha Mukantwari
- & Nadine Rujeni
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| Open AccessArtificial intelligence system reduces false-positive findings in the interpretation of breast ultrasound exams
Ultrasound is an important imaging modality for the detection and characterization of breast cancer, but it has been noted to have high false-positive rates. Here, the authors present an artificial intelligence system that achieves radiologist-level accuracy in identifying breast cancer in ultrasound imaging.
- Yiqiu Shen
- , Farah E. Shamout
- & Krzysztof J. Geras
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| Open AccessDevelopment of a model-inference system for estimating epidemiological characteristics of SARS-CoV-2 variants of concern
Quantification of the transmissibility and immune escape properties of SARS-CoV-2 variants is necessary to support pandemic planning. Here, the authors develop a model inference system to estimate these properties using incidence and mortality data for three variants of concern.
- Wan Yang
- & Jeffrey Shaman
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Article
| Open AccessAutomated bone mineral density prediction and fracture risk assessment using plain radiographs via deep learning
Dual-energy X-ray absorptiometry and the Fracture Risk Assessment Tool are recommended tools for osteoporotic fracture risk evaluation, but are underutilized. Here, the authors present an opportunistic tool to identify fractures, predict bone mineral density and evaluate fracture risk using plain pelvis and lumbar spine radiographs.
- Chen-I Hsieh
- , Kang Zheng
- & Chang-Fu Kuo
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Article
| Open AccessContact tracing is an imperfect tool for controlling COVID-19 transmission and relies on population adherence
Evaluations of the UK’s contact tracing programme have shown that it has had limited impact on COVID-19 control. Here, the authors show that with high levels of reporting and adherence, contact tracing could reduce transmission, but it should not be used as the sole control measure.
- Emma L. Davis
- , Tim C. D. Lucas
- & Petra Klepac
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| Open AccessA randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes
Community pharmacists are accessible healthcare providers with expertise in medication management. Here the authors show that a low-carbohydrate, low-energy diet implemented by community pharmacists reduced diabetes medication use and improved glucose control in people with type 2 diabetes.
- Cody Durrer
- , Sean McKelvey
- & Jonathan P. Little
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| Open AccessAutomatically disambiguating medical acronyms with ontology-aware deep learning
Disambiguating abbreviations is important for automated clinical note processing; however, deploying machine learning for this task is restricted by lack of good training data. Here, the authors show novel data augmentation methods that use biomedical ontologies to improve abbreviation disambiguation in many datasets.
- Marta Skreta
- , Aryan Arbabi
- & Michael Brudno
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| Open AccessA pre-registered short-term forecasting study of COVID-19 in Germany and Poland during the second wave
Forecasting models have been used extensively to inform decision making during the COVID-19 pandemic. In this preregistered and prospective study, the authors evaluated 14 short-term models for Germany and Poland, finding considerable heterogeneity in predictions and highlighting the benefits of combined forecasts.
- J. Bracher
- , D. Wolffram
- & Frost Tianjian Xu
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| Open AccessGlobal spread of Salmonella Enteritidis via centralized sourcing and international trade of poultry breeding stocks
Salmonella enterica serotype Enteritidis is a pathogen of poultry that can cause outbreaks in humans. Here the authors use genomic and trade data to investigate a pandemic in the 1980s, finding evidence that international trade of breeding stocks led to global spread of the pathogen.
- Shaoting Li
- , Yingshu He
- & Xiangyu Deng
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Article
| Open AccessDeep neural network-estimated electrocardiographic age as a mortality predictor
The electrocardiogram (ECG) is the most commonly used exam for the screening and evaluation of cardiovascular diseases. Here, the authors propose that the age predicted by artificial intelligence from the raw ECG tracing can be a measure of cardiovascular health and provide prognostic information.
- Emilly M. Lima
- , Antônio H. Ribeiro
- & Antonio Luiz P. Ribeiro
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Article
| Open AccessBattery-free, wireless soft sensors for continuous multi-site measurements of pressure and temperature from patients at risk for pressure injuries
Uninterrupted monitoring of pressure and temperature at skin interfaces can help to minimize the potential for pressure injuries in hospitalized or bedridden patients. Here, the authors introduce a soft, skin-mountable sensor that can continuously provide readings via antennas mounted under bedding, and demonstrate the functionality and robustness of the devices on patients.
- Yong Suk Oh
- , Jae-Hwan Kim
- & John A. Rogers
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| Open AccessThe risk of indoor sports and culture events for the transmission of COVID-19
Mass gathering events represent a risk for transmission of SARS-CoV-2. Here, the authors describe an experimental indoor test event in which individual contacts were measured and use aerosol and epidemiological modelling to evaluate transmission risks of different types of restrictions in the arena.
- Stefan Moritz
- , Cornelia Gottschick
- & Rafael Mikolajczyk
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Article
| Open AccessEtiological and epidemiological features of acute respiratory infections in China
China operates a national surveillance program for acute respiratory infections and sampled over 200,000 patients between 2009–2019. Here, the authors present results from this program and describe patterns by age, pathogen type, presence of pneumonia, and season.
- Zhong-Jie Li
- , Hai-Yang Zhang
- & Jun Wang
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Article
| Open AccessHigh COVID-19 transmission potential associated with re-opening universities can be mitigated with layered interventions
Reopening of universities to students following COVID-19 restrictions risks increased transmission due to high numbers of social contacts and the potential for asymptomatic transmission. Here, the authors use a mathematical model with social contact data to estimate the impacts of reopening a typical non-campus based university in the UK.
- Ellen Brooks-Pollock
- , Hannah Christensen
- & Leon Danon
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Article
| Open AccessDeep learning-based transformation of H&E stained tissues into special stains
Performing multiple histological stains on a biopsy can be costly and time consuming. Here the authors present a method for the digital transformation of H&E stained tissue into special stains (e.g., PAS, Masson’s Trichrome and Jones silver stain), and demonstrate that it improves diagnoses over the use of H&E only.
- Kevin de Haan
- , Yijie Zhang
- & Aydogan Ozcan
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Article
| Open AccessTracking the introduction and spread of SARS-CoV-2 in coastal Kenya
SARS-CoV-2 was first detected in Kenya in March 2020 and there was evidence of local transmission in the following months. Here, the authors characterise the early stages of the epidemic in coastal Kenya using phylogenetics and find evidence of multiple strain importations from international points of entry.
- George Githinji
- , Zaydah R. de Laurent
- & Charles N. Agoti
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| Open AccessDetection and characterization of the SARS-CoV-2 lineage B.1.526 in New York
West and colleagues develop the Variant Database software tool for examination of changing Spike mutations in SARS-CoV-2 genomes. The authors use this to detect emerging lineages of SARS-CoV-2 in New York and report the rapid spread of the B.1.526 lineage in the city.
- Anthony P. West Jr.
- , Joel O. Wertheim
- & Pamela J. Bjorkman
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Article
| Open AccessCOVID-19 spread, detection, and dynamics in Bogota, Colombia
Detailed information on SARS-CoV-2 infection rates in Latin America by occupation, socioeconomic group and geographic area are rarely available. Here, the authors provide these estimates for in Bogota, Colombia using data from a sentinel surveillance scheme, and find that over half the population had been infected by March 2021.
- Rachid Laajaj
- , Camilo De Los Rios
- & Duncan Webb
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Article
| Open AccessTime-varying optimization of COVID-19 vaccine prioritization in the context of limited vaccination capacity
In the context of limited supply, strategies for optimising allocation of COVID-19 vaccines are needed. Here, the authors explore time-varying strategies that adapt to the epidemiological situation and simultaneously optimise for multiple objectives including reducing numbers of infections, hospitalisations, and deaths.
- Shasha Han
- , Jun Cai
- & Hongjie Yu
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Article
| Open AccessHeatstroke predictions by machine learning, weather information, and an all-population registry for 12-hour heatstroke alerts
In the context of climate change, heatstroke is expected to become an increasingly relevant public health concern. Here, the authors develop and validate prediction models for the number of all heatstroke cases in different cities in Japan.
- Soshiro Ogata
- , Misa Takegami
- & Kunihiro Nishimura
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Matters Arising
| Open AccessTransplantation of discarded livers: the complementary role of normothermic regional perfusion
- Chris J. C. Johnston
- , Ahmed E. Sherif
- & Gabriel C. Oniscu